Over recent years, research in the synthesis of a wide range of structurally diverse .beta.-lactam antibiotics has substantially intensified. Much emphasis has centered upon the preparation of novel bicyclic .beta.-lactam antibiotics that differ from naturally occurring penicillins and cephalosporins not only in the structure of the C-6 or C-7 side chain or, in the case of cephalosporins, in the C-3 group, but also in the identity of the ring hetero-atom (i.e., oxygen, nitrogen, or carbon in place of sulfur). In the continuing search for such novel .beta.-lactam antibiotics, researchers have prepared a wide range of mono- and bicyclic .beta.-lactam intermediates.
The instant invention is directed to a process for preparing .beta.-lactam-containing bicyclic compounds useful as intermediates to .beta.-lactam antibiotics. More particularly, the instant invention is directed to a process for preparing compounds of the formulae ##STR3## in which Y is hydrogen or hydroxyl, which comprises reacting a sulfinic acid of the formula ##STR4## with an oxidizing agent; in which, in the above formulae, M is hydrogen, lithium, potassium, sodium, ammonium, or substituted ammonium;
R.sub.1 is hydrogen, lithium, potassium, sodium, ammnonium, substituted ammonium, or a carboxylic acid protecting group; and PA1 R is PA1 (a) C.sub.1 to C.sub.7 alkyl, C.sub.3 to C.sub.7 alkenyl, halomethyl, 4-carboxybutyl, 3-formylpropyl, 4-protected carboxybutyl, or 4-protected amino-4-protected carboxybutyl; PA1 (b) a group R.sub.2 in which R.sub.2 is 1,4-cyclohexadienyl, phenyl, or phenyl substituted on its ring by 1 or 2 groups selected from the group consisting of chloro, bromo, hydroxy, protected hydroxy, trifluoromethyl, C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, carboxy, carboxymethyl, hydroxymethyl, aminomethyl, and protected aminomethyl; PA1 (c) a group of the formula EQU R.sub.2 --(O).sub.m --CH.sub.2 -- PA1 in which R.sub.2 is as defined above and m is zero or one; PA1 (d) a group of the formula ##STR5## in which R.sub.3 is R.sub.2 as defined above, 2-thienyl, or 3-thienyl; and W is hydroxy, protected hydroxy, carboxy, protected carboxy, amino, or protected amino; or PA1 (e) a group of the formula EQU R.sub.4 --CH.sub.2 -- PA1 in which R.sub.4 is 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-thiazolyl, 5-tetrazolyl, or 1-tetrazolyl. PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(ammonium sulfinate)- 3-(S)-(p-toluylamido)-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(lithium sulfinate)- 3-(S)-(p-toluylamido)-4-oxo-azetidine; PA1 N-(lithium 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(lithium sulfinate)-3-(S)-(p-toluylamido)-4-oxo-azetidine; PA1 N-(lithium 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(lithium sulfinate)-3-(S)-(phenoxyacetamido)-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(ammonium sulfinate)-3-(S)-(phenoxyacetamido)-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(lithium sulfinate)- 3-(S)-(phenylacetamido)-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(ammonium sulfinate)-3-(S)-(phenylacetamido)-4-oxo-azetidine; PA1 N-(t-butyl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(sodium sulfinate)-3-(S)-(phenylacetamido)-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(ammonium sulfinate)-3-(S)-2-(thien-2-yl)acetamido-4-oxo-azetidine; PA1 N-(4-methoxybenzyl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-[2'-(R)-(lithium sulfinate)-3-(S)-[2-(thien-2-yl)acetamido-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(sodium sulfinate)-3-(S)-2-(fur-2-yl)acetamido-4-oxo-azetidine; PA1 N-(t-butyl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(tetraethylammonium sulfinate-3-(S)-[2-(tetrazol-1-yl)acetamido]-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(sodium sulfinate)-3-(S)-(2-amino-2-phenylacetamido)-4-oxo-azetidine; PA1 N-(tetramethylammonium 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(tetramethylammonium sulfinate)-3-(S)-[2-amino-2-(4-hydroxyphenyl)acetamido]-4-oxo-azetidine; PA1 N-(triphenylammonium 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2'-(R)-(triphenylammonium sulfinate)-3-(S)-[2-hydroxy-2-(3-chlorophenyl)acetamido]-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(potassium sulfinate)-3-(S)-[2-hydroxy-2-(4-hydroxyphenyl)acetamido]-4-oxoazetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(ammonium sulfinate)- 3-(S)-[D-(5-(2,4-dichlorobenzyloxycarbonylamino)-5-(benzhydrylcarboxylate)v aleramido-4-oxo-azetidine; PA1 N-[(4-methoxybenzyl) 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate]-2-(R)-(tetraethylammonium sulfinate)-3-(S)-[D-(5-amino)-5-(4-methoxybenzyl)carboxylate)valeramido)-4 -oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoic-ester)-2-(R)-(tetraethylammon ium sulfinate)-3-(S)-[D-(5-(2,4-dichlorobenzyloxycarbonyl))-5-(benzhydryl carboxylate)valeramido]-4-oxo-azetidine; PA1 N-[(4-methoxybenzyl) 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate]-2-(R)-(sodium sulfinate)-3-(S)-[D-(5-(2,4-dichlorobenzyloxycarbonylamino))-5-((4-methoxy benzyl)carboxylate)valeramido]-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(sodium sulfinate)-3-(S)-[D-(5-benzyloxycarbonylamino)-5-(benzhydryl carboxylate)valeramido]-4-oxo-azetidine; PA1 N-(4-methoxybenzyl) 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate]-2-(R)-(sodium sulfinate)-3-(S)-[D-(5-(4-methoxybenzyloxycarbonylamino))-5-((4-methoxyben zyl)carboxylate)valeramido]-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(potassium sulfinate)-3-(S)-[D-(5-(2,4-dichlorobenzyloxycarbonylamino))-5-(benzhydryl carboxylate)valeramido)-4-oxo-azetidine; PA1 N-(t-butyl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enate)-2-(R)-(sodium sulfinate)-3-(S)-[D-(5-(2,4-dichlorobenzyloxycarbonylamino))-5-((t-butyl)c arboxylate)valeramido]-4-oxo-azetidine; PA1 N-(t-butyl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(potassium sulfinate)-3-[D-(5-((4-methoxybenzyloxycarbonyl)amino)-5-((t-butyl)carboxy late)valeramido]-4-oxo-azetidine; PA1 N-(t-butyl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(sodium sulfinate)-3-(S)-(p-toluylamido)-4-oxo-azetidine; PA1 N-[(4-methoxybenzyl) 3'-hydroxymethyl-2'-yl-'-(R,S)-but-3'-enoate]-2-(R)-(sodium sulfinate)-3-(S)-(p-toluylamido)-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(potassium sulfinate)-3-(S)-(p-toluylamido)-4-oxo-azetidine; PA1 N-(potassium 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(potassium sulfinate) -3-(S)-(p-toluylamido)-4-oxo-azetidine; PA1 N-(potassium 3'-hydroxy-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(potassium sulfinate)-3-(S)-(2-phenoxyacetamido)-4-oxo-azetidine; PA1 N-(t-butyl 3'-hydroxymethyl-2'-2'-(R,S)-but-3'-enoate)-2-(R)-(sodium sulfinate)-3-(S)-(2-phenoxyacetamido)-4-oxo-azetidine; PA1 N-[(4-methoxybenzyl) 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate]-2-(R)-(sodium sulfinate)-3-(S)-(phenoxyacetamido)-4-oxo-azetidine; PA1 N-[(4-methoxybenzyl) 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate]-2-(R)-(sodium sulfinate)-3-(S)-(2-phenylacetamido)-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(potassium sulfinate)-3-(S)-(phenylacetamido)-4-oxo-azetidine; PA1 N-(t-butyl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(sodium sulfinate)-3-(S)-[2-(thien-2-yl)acetamido]-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(potassium sulfinate)-3-(S)-[2-(thien-2-yl)acetamido]-4-oxo-azetidine; PA1 N-[(4-methoxybenzyl) 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate]-2-(R)-(sodium sulfinate)-3-(S)-[2-(thien-2-yl)acetamido]-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(tri-n-butylammonium sulfinate)-3-(S)-(p-toluylamido)-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(sodium sulfinate)-3-(S)-[2-(thien-2-yl)acetamido]-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(sodium sulfinate)-3-(S)-[2-(phenoxyacetamido)]-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(sodium sulfinate)-3-(S)-(2-phenylacetamido)-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(sodium sulfinate)-3-(S)-[D-(5-(2,4-dichlorobenzoxycarbonylamino))-5-(benzylhydryl carboxylate)valeramido]-4-oxo-azetidine; PA1 N-(benzhydryl 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(sodium sulfinate)-3-(S)-(p-toluylamido)-4-oxo-azetidine; PA1 N-(sodium 3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoate)-2-(R)-(sodium sulfinate)-3-(S)-(2-phenoxyacetamido)-4-oxo-azetidine; PA1 N-(3'-hydroxymethyl-2'-yl-2'-(R,S)-but-3'-enoic acid)-2-(R)-(sulfinic acid)-3-(S)-(p-toluylamido)-4-oxo-azetidine; and the like. PA1 benzhydryl (2'(R,S))-2'-[(1R,5S)-3-[D-(4-protected amino-4-protected carboxybutyl)]-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl]-4'-hydro xy-3'-exomethylene butyrate; PA1 benzyl (2'(R,S))-2'-[(1R,5S)-3-(D-phenoxymethyl)-7-oxo-4-oxa-2,6-diazabicyclo[3.2 .0]hept-2-en-6-yl]-4'-hydroxy-3'-exomethylene butyrate; PA1 p-nitrobenzyl (2'(R,S))-2'-[(1R,5S)-3-(D-benzyl)-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept -2-en-6-yl]-4'-hydroxy-3'-exomethylene butyrate; PA1 p-methoxybenzyl (2'(R,S))-2'-[(1R,5S)-3-[D-(4-(benzyloxycarbonylamino))-4-(p-methoxybenzyl carboxylate)-but-1-yl]-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl]-4 '-hydroxy-3'-exomethylene butyrate; PA1 2,2,2-trichloroethyl (2'(R,S))-2'-[(1R,5S)-3-(D-phenyl)-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept -2-en-6-yl]-4'-hydroxy-3'-exomethylene butyrate; PA1 benzhydryl (2'(R,S))-2'-[(1R,5S)-3-(D-p-tolyl)-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hep t-2-en-6-yl]-4'-hydroxy-3'-exomethylene butyrate; PA1 p-nitrobenzyl (2'(R,S))-2'-[(1R5S)-3-(D-phenoxymethyl)-7-oxo-4-oxa-2,6-diazabicyclo[3.2. 0]hept-2-en-6-yl]-4'-hydroxy-3'-exomethylene butyrate; and the like.